Estef Vazquez

@estefvazquez.bsky.social

Such stuff that dreams are made of. Ph.D. Candidate @LIIGH_UNAM Interested in melanoma, immuno-oncology and spatial biology. ☕️🎸🎶

I lost my dad to stage IV prostate cancer. Christmas and New Year won't be the same. I feel like I could write a book about what I experienced, but I will just say this: patients are not data points. They are human beings whose suffering is real, profound, and shattering.

Recently @mbarse.bsky.social presented a journal club on a proof of concept methods paper by @daylab.bsky.social et al The pre-print at doi.org/10.1101/2024... is well written and we are interested in applying this method to future @lieberinstitute.bsky.social data. bsky.app/profile/mbar...

Accurate sample deconvolution of pooled snRNA-seq using sex-dependent gene expression patterns

Single-nucleus RNA sequencing (snRNA-seq) technology offers unprecedented resolution for studying cell type-specific gene expression patterns. However, snRNA-seq poses high costs and technical limitations, often requiring the pooling of independent biological samples and the loss of individual sample-level data. Deconvolution of sample identity using inherent features would enable the incorporation of pooled barcoding and sequencing protocols, thereby increasing data throughput and analytical sample size without requiring increases in experimental sample size and sequencing costs. In this study, we demonstrate a proof of concept that sex-dependent gene expression patterns can be leveraged for the deconvolution of pooled snRNA-seq data. Using previously published snRNA-seq data from the rat ventral tegmental area, we trained a range of machine learning models to classify cell sex using genes differentially expressed in cells from male and female rats. Models that used sex-dependent gene expression predicted cell sex with high accuracy (93-95%) and outperformed simple classification models using only sex chromosome gene expression (88-90%). The generalizability of these models to other brain regions was assessed using an additional published data set from the rat nucleus accumbens. Within this data set, model performance remained highly accurate in cell sex classification (90-92% accuracy) with no additional training. This work provides a model for future snRNA-seq studies to perform sample deconvolution using a two-sex pooled sample sequencing design and benchmarks the performance of various machine learning approaches to deconvolve sample identification from inherent sample features. ### Competing Interest Statement The authors have declared no competing interest. National Institute on Drug Abuse, DP1DA039650, R01DA053743, R01DA054714 National Institute of Mental Health, https://ror.org/04xeg9z08, R01MH114990 McKnight Foundation, https://ror.org/003ghvj67, Neurobiology of Brain Disorders Award

doi.org

Manisha Barse@mbarse.bsky.social · last yr.

Hi! Check my journal club talk: smart ML method to deconvolute pooled snRNA-seq using sex-specific expression🧬 Thanks @daylab.bsky.social & @rphillips3.bsky.social for this approach🙌 🎥 youtu.be/zpeCFwYfV3o 🛝 speakerdeck.com/manishabarse #snRNAseq #ML #Bioinformatics @lieberinstitute.bsky.social